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EGFR mutation: novel prognostic factor associated with immune infiltration in lower-grade glioma; an exploratory study

机译:EGFR突变:与较低级神经胶质瘤免疫浸润相关的新型预后因子;探索性研究

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BACKGROUND:Glioma is one of the most common type of primary central nervous system tumors. EGFR mutation, a common alteration occurs in various tumors, is not brought to the forefront in understanding and treating glioma at present.METHODS:In the present study, we demonstrated an immune infiltration related pattern of EGFR mutation in lower-grade glioma. In silico analyses were performed to investigate EGFR mutation and its biological effects and clinical values. GO and GSEA process were used as enrichment analysis. Infiltration levels of specific types of immune cells were estimated at TIMER database. Clinical data of patients were obtained from TCGA and were employed for survival analyses.RESULTS:Here we revealed that EGFR mutation leads to an up-regulation of immune response related pathways and dismal prognosis in lower-grade glioma. Infiltration of CD4+ T cells, neutrophils, macrophages, and dendritic cells were significantly increased in EGFR-mutant cases. Infiltration of specific types of immune cells were correlated with shorter survival time. PD-L1 was elevated in EGFR-mutant cases and correlated with infiltration level of CD4+ T cells, neutrophils and dendritic cells.CONCLUSION:EGFR mutation indicates increasing infiltration of specific types of immune cells and poor prognosis in lower-grade glioma. Alteration of immune microenvironment since the EGFR mutation might influence the survival of glioma. We also provided a novel evidence and indicator of PD-1 inhibitor application in glioma.
机译:背景:胶质瘤是最常见的主要中枢神经系统肿瘤之一。 EGFR突变,在各种肿瘤中发生常见的改变,在目前的理解和治疗神经胶质瘤中不会产生前沿。方法:在本研究中,我们证明了较低级胶质瘤中的EGFR突变的免疫渗透相关图案。在硅分析中进行以研究EGFR突变及其生物学效应和临床价值。 Go和GSEA过程用作富集分析。在定时器数据库中估计特异性免疫细胞的浸润水平。从TCGA获得患者的临床资料,用于存活分析。结果:在这里,我们揭示了EGFR突变导致免疫应答相关途径的上调和较低级胶质瘤中的爆破预后。在EGFR-突变病例中,CD4 + T细胞,中性粒细胞,巨噬细胞和树突细胞的浸润显着增加。特定类型的免疫细胞的浸润与较短的存活时间相关。 PD-L1在EGFR-突变病例中升高,与CD4 + T细胞,嗜中性粒细胞和树突细胞的浸润水平相关。结论:EGFR突变表明,较低级神经胶质瘤的特异性免疫细胞的渗透性增加以及较低级胶质瘤的预后差。由于EGFR突变可能影响胶质瘤的存活以来免疫微环境的改变。我们还提供了一种新的PD-1抑制剂在胶质瘤中的证据和指标。

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